At the end of life, being free from pain is among the top wishes for patients with advanced cancer. Despite multimodal palliative care, pain remains one of the most common symptoms for those with advanced cancer. Not only do high pain scores place patients at significant risk for emergency department visits and hospital readmission, high pain scores also are associated with increased suffering. For patients with advanced cancer who have failed interdisciplinary palliative care, minimally-invasive approaches to lesion spinal cord pain pathways can be considered. A particularly promising procedure is cordotomy, in which a lesion is placed in the spinothalamic tract to treat patients with unilateral arm, leg, or chest wall pain due to cancer. To understand the role of cordotomy in the palliative care setting, we have conducted a prospective clinical trial to determine the extent to which cordotomy can reduce advanced cancer pain. Sixteen patients with advanced cancer who had undergone optimized palliative care treatment were randomized to either undergo cordotomy or continue comprehensive palliative care. Six out of the seven patients randomized to cordotomy experienced greater than a 33% improvement in pain, while none of the nine patients randomized to continued palliative care improved. Based on this preliminary data, we hypothesize that cordotomy improves advanced cancer pain in selected patients undergoing concurrent interdisciplinary palliative care. Despite these encouraging results, it is well documented that surgical pain interventions can have a significant placebo effect. To control for placebo effects, we will undertake a single-institution, sham controlled clinical trial of cordotomy in patients with refractory cancer pain who are undergoing interdisciplinary palliative care. Our preliminary data also supports that cordotomy reduces the interference of pain on activities of daily living. We therefore hypothesize that cordotomy aligns well with patient goals towards the end of life. To test this hypothesis, we will use qualitative research methodology to study patients with refractory cancer pain who undergo cordotomy. Patients will be interviewed about their experience before, during, and after cordotomy. Finally, our data supports that MRI diffusion tensor imaging (DTI) can detect structural changes induced by cordotomy, and that DTI metrics correlate with pain improvement after cordotomy. We will test the hypothesis that post-procedure MRI can noninvasively predict pain outcome after cordotomy. Results from this study will be critical in establishing the role of cordotomy in the treatment of advanced cancer pain, and will facilitate the implementation of this treatment nationally.